Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study
Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are bi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.736969/full |
| _version_ | 1818974794554540032 |
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| author | Haruna Nonaka Shuya Kandori Satoshi Nitta Masanobu Shiga Yoshiyuki Nagumo Tomokazu Kimura Takashi Kawahara Hiromitsu Negoro Akio Hoshi Takahiro Kojima Koji Kawai Bryan J. Mathis Takuro Tamura Taka-Aki Sato Mariko Yamato Masayuki Noguchi Hiroyuki Nishiyama |
| author_facet | Haruna Nonaka Shuya Kandori Satoshi Nitta Masanobu Shiga Yoshiyuki Nagumo Tomokazu Kimura Takashi Kawahara Hiromitsu Negoro Akio Hoshi Takahiro Kojima Koji Kawai Bryan J. Mathis Takuro Tamura Taka-Aki Sato Mariko Yamato Masayuki Noguchi Hiroyuki Nishiyama |
| author_sort | Haruna Nonaka |
| collection | DOAJ |
| description | Solitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs. |
| first_indexed | 2024-12-20T15:45:43Z |
| format | Article |
| id | doaj.art-57ce08b87e9943b482f062106ff782ee |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-20T15:45:43Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-57ce08b87e9943b482f062106ff782ee2022-12-21T19:34:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-12-011110.3389/fonc.2021.736969736969Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case StudyHaruna Nonaka0Shuya Kandori1Satoshi Nitta2Masanobu Shiga3Yoshiyuki Nagumo4Tomokazu Kimura5Takashi Kawahara6Hiromitsu Negoro7Akio Hoshi8Takahiro Kojima9Koji Kawai10Bryan J. Mathis11Takuro Tamura12Taka-Aki Sato13Mariko Yamato14Masayuki Noguchi15Hiroyuki Nishiyama16Department of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Aichi Cancer Center Hospital, Nagoya, JapanDepartment of Urology, School of Medicine, International University of Health and Welfare, Narita, JapanInternational Medical Center, University of Tsukuba Affiliated Hospital, Tsukuba, JapanResearch and Development Centre for Precision Medicine, University of Tsukuba, Tsukuba, JapanResearch and Development Centre for Precision Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Urology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanSolitary fibrous tumors (SFT) are mesenchymal neoplasms with a favorable prognosis usually originating from the visceral pleura. Rarely, they may occur at various extrapleural sites and show malignant behavior coupled with dedifferentiation. NAB2-STAT6 fusion gene and STAT6 nuclear expression are biomarkers for diagnosis of SFT in addition to CD34, Bcl-2, and CD99. Furthermore, several reports have shown specific NAB2-STAT6 fusion variants and loss of STAT6 protein expression are associated with malignancy. We report a rare case of retroperitoneal SFT which rapidly progressed to death within 35 days after admission. Autopsy found a primary tumor containing both benign and malignant histologies, with multiple metastatic sites similar to the malignant, dedifferentiated tumor. STAT6 was detected in the primary differentiated tumor but not in the primary dedifferentiated tumor or lung/liver metastases. However, the NAB2-STAT6 fusion gene (NAB2ex6/STAT6ex16 variant) was detected in the primary tumor and lung/liver metastases. Intriguingly, fusion gene expression at the transcriptional level was downregulated in the dedifferentiated tumors compared to the differentiated tumor. We further performed target DNA sequencing and found gene mutations in TP53, FLT3, and AR in the dedifferentiated tumors, with TP53 mutations especially found among them. We demonstrate that downregulation of NAB2-STAT6 fusion gene at the transcriptional level is associated with malignant SFT for the first time. Moreover, the present study supports the idea that TP53 mutations promote malignancy in SFTs.https://www.frontiersin.org/articles/10.3389/fonc.2021.736969/fullmalignant solitary fibrous tumorNAB2-STAT6 fusion geneSTAT6 nuclear expressiontarget DNA sequencingTP53 mutation |
| spellingShingle | Haruna Nonaka Shuya Kandori Satoshi Nitta Masanobu Shiga Yoshiyuki Nagumo Tomokazu Kimura Takashi Kawahara Hiromitsu Negoro Akio Hoshi Takahiro Kojima Koji Kawai Bryan J. Mathis Takuro Tamura Taka-Aki Sato Mariko Yamato Masayuki Noguchi Hiroyuki Nishiyama Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study Frontiers in Oncology malignant solitary fibrous tumor NAB2-STAT6 fusion gene STAT6 nuclear expression target DNA sequencing TP53 mutation |
| title | Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study |
| title_full | Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study |
| title_fullStr | Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study |
| title_full_unstemmed | Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study |
| title_short | Case Report: Molecular Characterization of Aggressive Malignant Retroperitoneal Solitary Fibrous Tumor: A Case Study |
| title_sort | case report molecular characterization of aggressive malignant retroperitoneal solitary fibrous tumor a case study |
| topic | malignant solitary fibrous tumor NAB2-STAT6 fusion gene STAT6 nuclear expression target DNA sequencing TP53 mutation |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.736969/full |
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